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Toxin-Producing Klebsiella oxytoca in Healthy Infants: Commensal or Pathobiont?
Theresa M Greimel1, Laura Stampfer1, Eva Leitner2
1Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine.
Objectives:
Klebsiella oxytoca is a gastrointestinal pathobiont with the potential to produce the toxins tilivalline and tilimycin, which cause antibiotic-associated hemorrhagic colitis. Overgrowth of toxigenic K oxytoca has recently been implicated in necrotizing enterocolitis. K oxytoca colonizes 2-9% of healthy adults, however, there is no systematic data on colonization in healthy children. We investigated K oxytoca colonization and its toxigenic properties in healthy infants.
Methods:
We sampled stool of healthy infants and determined K oxytoca colonization using stool culture and PCR (pehX). Toxin in stool was measured with HPLC/high-resolution mass spectrometry. K oxytoca isolates were typed using multi-locus sequence typing (MLST) and K oxytoca toxin PCR (npsA/B). Cytotoxin production of isolates was analyzed by MTT assay.
Results:
K oxytoca was detected in 30 of 61 infants (49%) using stool culture and in 45 of 61 (73%) using PCR (pehX). Toxin marker PCR (npsA/B) was positive in 66% of stool samples positive for K oxytoca PCR. Stool toxin levels were too low for quantitation but traces of tilivalline were detected. Contrarily, 49% of K oxytoca isolates demonstrated toxicity in the MTT assay. MLST revealed 36 distinct sequence types affiliated with all known K oxytoca sequence type clusters (A, B1 and B2).
Conclusions:
More than 70% of healthy infants were colonized with K oxytoca. Toxin quantities in stool of colonized healthy infants were below detection level, yet half of the isolates produced toxin in vitro demonstrating their pathobiont potential. The high occurrence of toxigenic K oxytoca in healthy infants has to be considered for future disease association studies.
Insights
Most healthy infants are colonized with Klebsiella oxytoca, a bacterium that can produce toxins. While toxin levels were low in infant stool, many isolates showed toxicity in lab tests, indicating potential health risks.
Area of Science:
- Microbiology
- Gastroenterology
- Pediatrics
Background:
- Klebsiella oxytoca is a gastrointestinal pathobiont capable of producing toxins like tilivalline and tilimycin.
- Toxigenic K. oxytoca overgrowth is linked to antibiotic-associated hemorrhagic colitis and necrotizing enterocolitis.
- While adult colonization rates are known (2-9%), data on healthy infants is lacking.
Purpose of the Study:
- To investigate the colonization prevalence of K. oxytoca in healthy infants.
- To assess the toxigenic potential of K. oxytoca strains colonizing infants.
- To characterize K. oxytoca isolates from healthy infants.
Main Methods:
- Stool samples from healthy infants were analyzed for K. oxytoca using culture and PCR (pehX).
- Toxin presence in stool was measured via HPLC/high-resolution mass spectrometry.
- K. oxytoca isolates underwent multi-locus sequence typing (MLST), toxin gene PCR (npsA/B), and cytotoxin analysis (MTT assay).
Main Results:
- K. oxytoca was detected in 73% of infants via PCR and 49% via culture.
- Toxin marker genes (npsA/B) were present in 66% of positive samples; trace tilivalline was detected.
- 49% of K. oxytoca isolates exhibited in vitro toxicity, and MLST identified 36 distinct sequence types.
Conclusions:
- A high prevalence (>70%) of K. oxytoca colonization exists in healthy infants.
- Despite low in-stools toxin levels, isolates demonstrate in vitro pathogenicity, highlighting their pathobiont potential.
- The frequent presence of toxigenic K. oxytoca in infants warrants consideration in future disease association studies.
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